Intrahippocampal Norleucine1-Angiotensin IV mitigates scopolamine-induced spatial working memory deficits

Depletion of cholinergic neurons in the hippocampus has been implicated in memory impairment and Alzheimer's Disease (AD). The brain angiotensin AT(4) receptor is co-localized with cholinergic neurons, and the AT4 receptor has also been implicated in cognitive processing. The current investigation used the spatial win-shift version of the radial arm maze to determine the involvement of AT4 receptors in spatial working memory formation. We initially established that intrahippocampal scopolamine significantly impaired the spatial working memory performance of Sprague-Dawley rats in the radial arm maze. We also demonstrated that subsequent intrahippocampal infusions of Norleucine(1)-Angiotensin IV (Nle(1)-AngIV) significantly prevented the scopolamine-induced deficit. Consistent with previously published data on long-term spatial memory, our findings suggest that activation of AT4 receptors can compensate for impaired spatial working memory resulting from compromised muscarinic acetylcholine receptor function. We further demonstrate that the hippocampus is a site of action for Nle(1)-AngIV-mediated cognitive improvement. (C) 2010 Elsevier Inc. All rights reserved.